Download C-EDGE Treatment Naïve (TN)

Phase 3
Treatment Naïve
Elbasvir-Grazoprevir in Treatment-Naïve HCV Genotype 1, 4 or 6
C-EDGE Treatment Naïve (TN)
Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Elbasvir-Grazoprevir in Treatment-Naïve HCV Genotype 1, 4 or 6
C-EDGE TN Study: Features
C-EDGE TN Trial
 Design: Randomized, placebo-controlled, parallel-group, phase 3 trial
using a fixed-dose combination of elbasvir-grazoprevir for 12 weeks in
treatment-naïve patients with GT 1, 4 or 6 chronic HCV
 Setting: 60 sites in United States, Europe, Australia, Scandinavia, & Asia
 Entry Criteria
- Chronic HCV: GT1=91%, GT4=6%, or GT6=3%
- 18 years or older
- HCV RNA ≥10,000 IU/mL
- No prior HCV treatment
- Patients with compensated cirrhosis accepted
 Primary End-Point: SVR12
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Elbasvir-Grazoprevir in Treatment-Naïve HCV Genotype 1, 4 or 6
C-EDGE TN: Study Design
Week
0
12
N=316
Elbasvir-Grazoprevir
N=105
Placebo
16
24
40
28
SVR12
Treatment-naïve
GT 1, 4 or 6
(N=421)
Elbasvir-Grazoprevir
SVR12
Randomized 3:1 ratio to immediate or deferred arm; stratified by cirrhosis, HCV genotype, subtype
After 4 weeks of follow-up, placebo recipients were unblinded and given elbasvir-grazoprevir open label
Drug Dosing
Elbasvir-Grazoprevir (50/100 mg): fixed dose combination; one pill once daily
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6
C-EDGE TN: Baseline Characteristics
Immediate Arm
(N=316)
Delayed Arm
(N=105)
All Patients
(N=421)
Age, mean
52
54
53
Male, %
54
53
54
Race, %
Asian
Black
White
17
19
60
12
17
70
16
18
63
HCV genotype, n (%)
1a
1b
4
6
157 (50)
131 (42)
18 (6)
10 (3)
54 (51)
40 (38)
8 (8)
3 (3)
211 (50)
171 (41)
26 (6)
13 (3)
HCV RNA >800,000 IU/ml, %
222 (70)
66 (63)
288 (68)
IL28B non-CC, %
66
64
65
Fibrosis stage, %
F0-2
F3
F4
67
11
22
66
13
21
66
12
22
Baseline Characteristic
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6
C-EDGE TN: Results
C-EDGE TN: SVR12 Results by Genotype
Patients with SVR12 (%)
100
95
99
100
92
80
80
60
40
20
0
299/316
144/157
129/131
18/18
8/10
All
GT 1a
GT 1b
GT 4
GT 6
Primary efficacy analysis included all patients who received ≥1 dose of drug.
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6
C-EDGE TN: Results
C-EDGE TN: SVR12 by Presence of Cirrhosis or High HCV RNA Level
100
97
100
231/246
68/70
94/94
205/222
No Cirrhosis
Cirrhosis
≤800K IU/mL
>800K IU/mL
Patients (%) with SVR 12
94
92
80
60
40
20
0
Presence of Cirrhosis
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Baseline HCV RNA
Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6
C-EDGE TN: Results
Baseline NS5A Resistance-Associated Variants and SVR12 in GT1
Baseline NS5A RAVs*
No Baseline NS5A RAVs
Patients (%) with SVR 12
100
99
100
94
80
60
58
40
20
11/19
133/135
17/18
112/112
0
Genotype 1a
Genotype 1b
*Patients with baseline GT1a RAVs with a ≤5-fold shift to elbasvir: SVR12=90% (9 of 10)
*Patients with baseline GT1a RAVs with a >5-fold shift to elbasvir: SVR12=22% (2 of 9)
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6
C-EDGE TN: Results
Baseline NS3/4A Resistance-Associated Variants and SVR12 in GT1
Baseline NS3/4A RAVs
No Baseline NS3/4A RAVs
Patients (%) with SVR 12
100
97
96
100
89
80
60
40
20
0
83/86
58/65
Genotype 1a
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
24/25
104/104
Genotype 1b
Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6
C-EDGE TN: Adverse Events
Elbasvir-Grazoprevir
Adverse Event (AE)
Immediate
(n=316)
Deferred (Placebo)
(n=105)
3 (0.9%)
1 (1%)
9 (3%)
3 (3%)
Deaths
2 (0.6%)§
0
Any AE in ≥10% of patients
Headache
Fatigue
52 (17%)
49 (16%)
19 (18%)
18 (17%)
Laboratory AEs
ALT >5 x baseline
AST >5 x baseline
Total bilirubin elevation >5 x baseline
Grade 3 or 4 hemoglobin
Grade 3 or 4 neutrophils
Grade 3 or 4 creatinine
3 (0.9%)
1 (0.3%)
1 (0.3%)
0
1 (0.3%)
0
0
0
0
0
1 (1%)
0
Discontinuation due to AE
Serious AEs
§ Neither
death was considered to be study-related.
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
Elbasvir-Grazoprevir in Treatment-Naïve HCV GT 1, 4 or 6
C-EDGE TN: Conclusions
Conclusions: “Grazoprevir-elbasvir achieved high SVR12 rates in
treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4,
or 6 infection. This once-daily, all-oral, fixed-combination regimen
represents a potent new therapeutic option for chronic HCV infection.”
Source: Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.